       Document 0147
 DOCN  M9550147
 TI    In vivo model of HIV infection of the human brain.
 DT    9505
 AU    Achim CL; Miners DK; Burrola PG; Martin FC; Wiley CA; University of
       Pittsburgh Medical Center, Division of; Neuropathology, Pa.
 SO    Dev Neurosci. 1993;15(6):423-32. Unique Identifier : AIDSLINE
       MED/95136894
 AB    Approximately one quarter of the AIDS patients have severe HIV
       encephalitis with diffuse neuronal damage that may be mediated by immune
       factors secreted by CNS macrophages. Based on an in vitro brain
       microsphere model, we developed an in vivo system in which human
       embryonic brain tissue survives for several months in the interscapular
       fat pad of SCID mice. Coculture of human brain tissue with macrophages
       prior to transplantation resulted in infiltration of the microspheres by
       activated macrophages. When the macrophages were infected in vitro with
       a neurotropic HIV strain, viral particles were detected in vivo up to 3
       months after transplantation. HIV-infected transplants contained
       multinucleated giant cells similar to those seen in HIV encephalitis.
       However, the neuroglial component degenerated in the fat pad of SCID
       mice. The absence of synaptogenesis in the human transplants suggests
       that the murine fat pad lacks adequate stimuli or support for human
       neuronal differentiation. To study neurologic damage associated with HIV
       infection, sites of implantation that stimulate synaptogenesis (e.g.
       murine CNS) will need to be explored. Based on these findings we
       conclude that transplantation of brain microspheres with HIV-infected
       macrophages into SCID mice may be an achievable model of HIV
       encephalitis.
 DE    Animal  AIDS Dementia Complex/*PATHOLOGY/VIROLOGY
       Brain/*PATHOLOGY/VIROLOGY  Brain Tissue Transplantation  Cell
       Transplantation  Cells, Cultured  Fetal Tissue Transplantation  Human
       Immunohistochemistry  Macrophages/IMMUNOLOGY  Male  Mice  Mice, SCID
       Microscopy, Electron  Microspheres  Models, Biological  Nerve
       Degeneration  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Transplantation, Heterologous  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

